Effect of NSAID Use on Bone Healing in Pediatric Fractures: A Preliminary, Prospective, Randomized, Blinded Study.

BACKGROUND: This study aimed to investigate if nonsteroidal anti-inflammatory drugs (NSAIDs) used in the acute phase of bone healing in children with fractures result in delayed union or nonunion as compared with patients who do not take NSAIDs for pain control during this same time period. METHODS: In this prospective, randomized, parallel, single-blinded study, skeletally immature patients with long bone fractures were randomized to 1 of 2 groups for their postfracture pain management. The NSAID group was prescribed weight-based ibuprofen, whereas the control group was not allowed any NSAID medication and instead prescribed weight-based acetaminophen. Both groups were allowed to use oxycodone for breakthrough pain. The primary outcome was fracture healing assessed at 2, 6, and 10 weeks. RESULTS: One-hundred-two patients were enrolled between February 6, 2014 and September 23, 2016. Ninety-five patients (with 97 fractures) completed a 6-month follow-up (46 patients with 47 fractures in the control group and 49 patients 50 fractures in the NSAID group). None achieved healing at 1 to 2 weeks. By 6 weeks, 37 of 45 patients (82%) of control group and 46 out of 50 patients (92%) of ibuprofen group had healed fractures (P=0.22). At 10 to 12 week follow-up, 46 (98%) of the control group fractures were healed and 50 (100%) of the ibuprofen group fractures were healed. All were healed by 6 months. Healing was documented at a mean of 40 days in the control group and 31 days in the ibuprofen group (P=0.76). The mean number of days breakthrough oxycodone was used was 2.4 days in the control group and 1.9 days in the NSAID group (P=0.48). CONCLUSION: Ibuprofen is an effective medication for fracture pain in children and its use does not impair clinical or radiographic long bone fracture healing in skeletally immature patients. LEVEL OF EVIDENCE: Level I-therapeutic.

Enhanced Subchondroplasty Treatment for Post-Traumatic Cartilage and Subchondral Bone Marrow Lesions in a Canine Model.

This study characterizes outcomes associated with subchondroplasty (SCP) versus SCP enhanced with platelet-rich plasma (PRP) or bone marrow aspirate concentrate (BMC) treatment of impact-induced subchondral bone marrow lesions (BML) using a validated preclinical canine model. With IACUC approval, purpose-bred research hounds (n = 24) underwent arthroscopic impact injury (40 N) to both medial femoral condyles. At 3 months, functional assessments, arthroscopy, and magnetic resonance imaging (MRI) were performed. One knee in each dog (n = 24; n = 12 per endpoint) was randomly assigned to SCP with the other knee randomly assigned to SCP + PRP, SCP + BMC or sham injection (control) (n = 8 per group; n = 4 per endpoint). Dogs were evaluated at 6 and 12 months after treatment using functional assessments, radiography, arthroscopy, and MRI and humanely euthanatized at 6 or 12 months after treatment for histologic assessments. At 6 months post-treatment, comfortable range-of-motion (CROM) was higher (p < 0.04) in SCP + PRP and SCP + BMC knees compared with controls. At 1 year post-treatment, %Total Pressure Index was higher (p = 0.036) in SCP + BMC compared with controls, pain was lower (p < 0.05) in SCP + BMC and SCP + PRP compared with SCP and controls, and CROM was higher (p < 0.05) in SCP + BMC and SCP + PRP compared with SCP and controls. Knees treated with SCP + PRP and SCP + BMC had better (p < 0.05) MRI grades than SCP and controls. No statistically significant differences in arthroscopic or histologic pathology were noted. Clinical significance: Biologics added to SCP treatment may further enhance its beneficial effects by improving range-of-motion, pain severity, and limb loading through 1 year after treatment. However, these benefits must be considered alongside cost, logistics, and treatment availability. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:740-746, 2020.

Return to Play after Patellar Stabilization.

PURPOSE OF REVIEW: The purpose of this review is to evaluate the existing literature regarding return to play (RTP) and return to prior performance (RPP) following patellar stabilization surgery. It will also discuss suggested guidelines regarding RTP, and finally, to encourage future patellofemoral instability research to report and publish results of RTP rates using standardized RTP guidelines. RECENT FINDINGS: There is a lack of validation and universal adoption of standardized RTP guidelines. This has led to a dearth of high-quality studies on RTP and RPP after patellar stabilization. The best available studies to date would suggest high RTP rates (84%-100%), average RPP rates (33%-77%), and a highly variable timeframe for return (3-12 months). Patellofemoral instability can be a persistent and challenging problem, particularly in the young and active population for which it most often occurs. Much of the previous studies on patellofemoral instability evaluated success and failure as prevention of recurrent dislocation. However, prevention of recurrence alone may not be enough for many patients. The best available data on RTP and RPP following patellofemoral instability is based on lower quality of evidence studies, expert opinion, and published societal guidelines. Future research on this topic should include clinical validation of the International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine (ISAKOS) RTP guidelines and reporting of outcomes based on these guidelines in patellofemoral instability publications.

Human growth hormone may be detrimental when used to accelerate recovery from acute tendon-bone interface injuries.

BACKGROUND: There have been few scientific studies that have examined usage of human growth hormone to accelerate recovery from injury. The hypothesis of this study was that human growth hormone would accelerate tendon-to-bone healing compared with control animals treated with placebo in a rat model of acute rotator cuff injury repair. METHODS: Seventy-two rats underwent repair of acute rotator cuff injuries and were randomized into the following postoperative dosing regimens: placebo, and human growth hormone at 0.1, 1, 2, 5, and 10 mg/kg/day, administered subcutaneously once per day for fourteen days (Protocol 1). An additional twenty-four rats were randomized to receive either (1) placebo or (2) human growth hormone at 5 mg/kg, administered subcutaneously twice per day for seven days preoperatively and twenty-eight days postoperatively (Protocol 2). All rats were killed twenty-eight days postoperatively. Mechanical testing was performed. Ultimate stress, ultimate force, stiffness, energy to failure, and ultimate distension were determined. RESULTS: For Protocol 1, analysis of variance testing showed no significant difference between the groups with regard to ultimate stress, ultimate force, stiffness, energy to failure, or ultimate distension. In Protocol 2, ultimate force to failure was significantly worse in the human growth hormone group compared with the placebo group (21.1 ± 5.85 versus 26.3 ± 5.47 N; p = 0.035). Failure was more likely to occur through the bone than the tendon-bone interface in the human growth hormone group compared with the placebo group (p = 0.001). No significant difference was found for ultimate stress, ultimate force, stiffness, energy to failure, or ultimate distension between the groups in Protocol 2. CONCLUSIONS: In this rat model of acute tendon-bone injury repair, daily subcutaneous postoperative human growth hormone treatment for fourteen days failed to demonstrate a significant difference in any biomechanical parameter compared with placebo. Furthermore, subcutaneous administration of 5 mg/kg of human growth hormone twice daily from seven days preoperatively until twenty-eight days postoperatively demonstrated lower loads to ultimate failure and a higher risk of bone fracture failure compared with placebo.

Increased anxiety-like behavior of rats during amphetamine withdrawal is reversed by CRF2 receptor antagonism.

Withdrawal from psychostimulants increases anxiety states, and amphetamine-treated rats show increased CRF(2) receptors in the serotonergic cell body region, the dorsal raphe nucleus (dRN). In the current study, amphetamine (2.5 mg/kg, i.p., 14 days) pre-treated rats spent less time in open arms of the elevated plus maze compared saline pre-treated rats at both 24h or 2 weeks of withdrawal, and CRF(2) receptor antagonism (ASV-30; 2 microg/0.5 microl) within the dRN reversed the effects of amphetamine withdrawal on anxiety-like behavior. Overall, results suggest that CRF(2) receptor antagonism may be a novel pharmacological target for anxiety states during drug withdrawal.